Protocol for a phase 3 trial to evaluate the effectiveness and safety of a heterologous, two-dose vaccine for Ebola virus disease in the Democratic Republic of the Congo
Deborah Watson-Jones,
Shelley Lees,
Brian Greenwood,
Daniel G Bausch,
Peter G Smith,
Chrissy H Roberts,
Nathalie Imbault,
Anton Camacho,
W John Edmunds,
Eric Delaporte,
Melanie Saville,
John Johnson,
Ira M Longini,
Hugo Kavunga-Membo,
Rebecca F Grais,
Steve Ahuka,
Natalie Roberts,
Edward M Choi,
Tansy Edwards,
Maarten Leyssen,
Bart Spiessens,
Kerstin Luhn,
Macaya Douoguih,
Richard Hatchett,
Jean-Jacques Muyembe,
W John Edmunds,
Daniela Manno,
Rebecca Grais,
Susan Rattigan,
Grace Mambula,
Patient Mumbere Kighoma,
Marie Burton,
Gerald Voss
Affiliations
Deborah Watson-Jones
2 Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK
Shelley Lees
Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK
Brian Greenwood
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK
Daniel G Bausch
UK Public Health Rapid Support Team, London School of Hygiene & Tropical Medicine/Public Health England, London, UK
Peter G Smith
MRC International Statistics and Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK
Chrissy H Roberts
Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK
Nathalie Imbault
Anton Camacho
Epicentre, Paris, Île-de-France, France
W John Edmunds
1 Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
Eric Delaporte
Melanie Saville
CEPI, Oslo, Norway
John Johnson
Ira M Longini
Hugo Kavunga-Membo
L’Institut National de Recherche Biomédicale, Goma, Democratic Republic of the Congo
Rebecca F Grais
Epicentre, Paris, France
Steve Ahuka
L’Institut National de Recherche Biomédicale, Goma, Democratic Republic of the Congo
Natalie Roberts
Australian Institute of Health Innovation, Macquarie University, Sydney, New South Wales, Australia
Edward M Choi
London School of Hygiene & Tropical Medicine, London, UK
Tansy Edwards
London School of Hygiene & Tropical Medicine, London, UK
Maarten Leyssen
Janssen Vaccines and Prevention BV, Leiden, Zuid-Holland, The Netherlands
Bart Spiessens
Janssen Vaccines and Prevention BV, Leiden, Zuid-Holland, The Netherlands
Kerstin Luhn
Janssen Vaccines and Prevention BV, Leiden, Zuid-Holland, The Netherlands
Macaya Douoguih
Janssen Vaccines and Prevention BV, Leiden, Zuid-Holland, The Netherlands
Richard Hatchett
Coalition for Epidemic Preparedness Innovations, Oslo, Norway
Jean-Jacques Muyembe
L’Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo
W John Edmunds
Daniela Manno
Rebecca Grais
4 Department of Research, Epicentre, Paris, France
Introduction Ebola virus disease (EVD) continues to be a significant public health problem in sub-Saharan Africa, especially in the Democratic Republic of the Congo (DRC). Large-scale vaccination during outbreaks may reduce virus transmission. We established a large population-based clinical trial of a heterologous, two-dose prophylactic vaccine during an outbreak in eastern DRC to determine vaccine effectiveness.Methods and analysis This open-label, non-randomised, population-based trial enrolled eligible adults and children aged 1 year and above. Participants were offered the two-dose candidate EVD vaccine regimen VAC52150 (Ad26.ZEBOV, Modified Vaccinia Ankara (MVA)-BN-Filo), with the doses being given 56 days apart. After vaccination, serious adverse events (SAEs) were passively recorded until 1 month post dose 2. 1000 safety subset participants were telephoned at 1 month post dose 2 to collect SAEs. 500 pregnancy subset participants were contacted to collect SAEs at D7 and D21 post dose 1 and at D7, 1 month, 3 months and 6 months post dose 2, unless delivery was before these time points. The first 100 infants born to these women were given a clinical examination 3 months post delivery. Due to COVID-19 and temporary suspension of dose 2 vaccinations, at least 50 paediatric and 50 adult participants were enrolled into an immunogenicity subset to examine immune responses following a delayed second dose. Samples collected predose 2 and at 21 days post dose 2 will be tested using the Ebola viruses glycoprotein Filovirus Animal Non-Clinical Group ELISA. For qualitative research, in-depth interviews and focus group discussions were being conducted with participants or parents/care providers of paediatric participants.Ethics and dissemination Approved by Comité National d’Ethique et de la Santé du Ministère de la santé de RDC, Comité d'Ethique de l'Ecole de Santé Publique de l’Université de Kinshasa, the LSHTM Ethics Committee and the MSF Ethics Review Board. Findings will be presented to stakeholders and conferences. Study data will be made available for open access.Trial registration number NCT04152486.
